Increasing Organ availability: From Machine Perfusion to Donors after Cardiac Death. Ayyaz Ali

Transcription

1 Increasing Organ availability: From Machine Perfusion to Donors after Cardiac Death Ayyaz Ali

2 No relevant financial disclosures 2

3 Heart Transplantation - Activity 3

4 Donor Heart Preservation Static preservation with cold storage Cornerstone of organ preservation Simplicity is major advantage Organs can be preserved for only limited periods of time across defined distances Substantial incidence of primary graft dysfunction 4

5 Machine Perfusion of the Donor Heart First generation of devices approved for clinical use Likely to have a prominent role in donor heart preservation in the future Portable ex-vivo perfusion devices designed to perfuse the donor heart with normothermic blood Aim to improve organ quality, validate organ viability and increase utilization of donor hearts Maintenance of donor heart in a near-physiologic state outside of the human 5

6 Transmedics Organ Care System Portable ex-vivo perfusion device Only current fully portable technology for ex-vivo donor heart perfusion In use in several transplant centers in Europe, Australia and Canada Being tested in clinical trials within the U.S.A. 6

7 Transmedics Organ Care System l of donor blood collected prior to aortic cross-clamping Donor heart retrieved in standard fashion followed by instrumentation onto device Oxygenated blood delivered into donor aortic root via pulsatile pump Maintain aortic pressure mm Hg and coronary flow rate of l/min Wireless monitor controls perfusion rate of OCS and displays aortic pressure, coronary flow rate, hematocrit, temperature and oxygen saturation 7

8 Clinical Evaluation PROTECT I First-in-man multicenter prospective single arm non-randomized safety and performance study conducted in UK and Germany Primary endpoint: 7-day survival Secondary endpoint: 30-day patient and graft survival 20 eligible hearts transplanted All 20 patients met primary endpoint and demonstrated 30-day survival PROCEED I Prospective multicenter single arm non-randomized FDA safety and performance study First U.S. clinical trial of OCS device 14 hearts instrumented onto OCS, 13 transplanted and one declined after assessment 11/13 recipients reached 7- and 30-day survival endpoints 2 patients suffered PGD with one re-transplanted and one death Based on combination of PROTECT I and PROCEED I FDA granted approval for PROCEED II 8

9 Clinical Evaluation PROCEED II Prospective, randomized, international multicenter, non-inferiority trial Comparison of safety and efficacy of OCS to cold storage Primary endpoint: 30-day patient and graft survival Completion of recruitment in September recipients transplanted Primary outcome of 30-day patient survival achieved in 93% of patients randomized to OCS device vs. 96% in cold storage group EXPAND Prospective multicenter international single arm study to evaluate safety and outcome of heart transplantation using extended criteria donor hearts preserved with the OCS Phase 3 clinical trial to assess ability to recover donor hearts which do not meet standard acceptance criteria for transplantation Study commenced in eight participating centers in September 2015 and due to conclude in November 2017, aim to enroll 75 patients 9

10 PROCEED II Interim analysis Ischemic time and clinical results 10

11 DCD Donors DCD donors UK DCD donors UNOS 11

12 DCD Heart Transplantation 12

13 2006 Successful resuscitation of human DCD heart following ECMO reperfusion 13

14 2009 Cardiac resuscitation in a rodent DCD model Baseline Circulatory arrest Cardiac resuscitation 14

15 2009 Cardiac resuscitation in a rodent DCD model DCD Brainstem death 15

16 2010 Cardiac resuscitation in a porcine DCD model DCD Brainstem death 16

17 Myocardial energetics 17

18 Porcine Orthotopic DCD heart transplantation 18

19 Porcine Orthotopic DCD heart transplantation DCD Brainstem death LV RV 19

20 Porcine Orthotopic DCD heart transplantation 20

21 Human DCD Heart Resuscitation 21

22 Clinical DCD Heart Transplantation 29 DCD heart transplants at Papworth Hospital since introduction of clinical program in March day survival: 100% 90-day survival: 96% Has resulted in 39% increase in heart transplantation at our institution 2 procurement methods NRP/ECMO Direct procurement 22

23 Inclusion & Exclusion Criteria 23

24 Donor Demographics 24

25 Recipient Demographics 25

26 DCD Heart: Ischemia & reperfusion 26

27 DCD Heart Transplant Outcomes 27

28 Conclusion Machine perfusion of the donor heart is likely to have a major role in the future of heart transplantation This technology is expected to aid in the recovery and resuscitation of extended criteria donor hearts Early results of DCD heart transplantation suggest that results are comparable to heart transplantation from BSD cadaveric donors 28

29 Thank You